Antiretroviral Pharmacology in Mucosal Tissues

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Abstract

Strategies to prevent HIV infection using preexposure prophylaxis are required to curtail the HIV pandemic. The mucosal tissues of the genital and rectal tracts play a critical role in HIV acquisition, but antiretroviral (ARV) disposition and correlates of efficacy within these tissues are not well understood. Preclinical and clinical strategies to describe ARV pharmacokinetic–pharmacodynamic relationships within mucosal tissues are currently being investigated. In this review, we summarize the physicochemical and biologic factors influencing ARV tissue exposure. Furthermore, we discuss the necessary steps to generate relevant pharmacokinetic–pharmacodynamic data and the challenges associated with this process. Finally, we suggest how preclinical and clinical data might be practically translated into optimal preexposure prophylaxis dosing strategies for clinical trials testing using mathematical modeling and simulation.

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